Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer
Name
cd-23-1336.pdf
Description
Published version
Size
44.12 MB
Format
Adobe PDF
Checksum (MD5)
143d9a18ea38a3c43da918244f80c17a
Author(s)
Mangena, Vamsi
Chanoch-Myers, Rony
Sartore, Rafaela
Paulsen, Bruna
Gritsch, Simon
Weisman, Hannah
Hara, Toshiro
Breakefield, Xandra O
Breyne, Koen
Regev, Aviv
Date Issued
October 7, 2024
Journal
Cancer Discovery
Publisher
American Association for Cancer Research
Citation
Vamsi Mangena, Rony Chanoch-Myers, Rafaela Sartore, Bruna Paulsen, Simon Gritsch, Hannah Weisman, Toshiro Hara, Xandra O. Breakefield, Koen Breyne, Aviv Regev, Kwanghun Chung, Paola Arlotta, Itay Tirosh, Mario L. Suva; Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer. Cancer Discov 2024.
Version
Final published version
Abstract
Glioblastoma is characterized by heterogeneous malignant cells that are functionally integrated within the neuroglial microenvironment. Here, we model this ecosystem by growing glioblastoma into long-term cultured human cortical organoids that contain the major neuroglial cell types found in the cerebral cortex. Single-cell RNA-seq analysis suggests that, compared to matched gliomasphere models, glioblastoma cortical organoids (GCO) more faithfully recapitulate the diversity and expression programs of malignant cell states found in patient tumors. Additionally, we observe widespread transfer of glioblastoma transcripts and GFP proteins to non-malignant cells in the organoids. Mechanistically, this transfer involves extracellular vesicles and is biased towards defined glioblastoma cell states and astroglia cell types. These results extend previous glioblastoma-organoid modeling efforts and suggest widespread intercellular transfer in the glioblastoma neuroglial microenvironment.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs
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DOI of Published Version
https://doi.org/10.1158/2159-8290.cd-23-1336
